Antibacterial phage, phage peptides and methods of use thereof
Inventors
Da Costa Garcia, Miguel Angelo • Sousa De Sao Jose, Carlos Jorge • Rodrigues Leandro, Clara Isabel • Dias Antunes Marcal Da Silva, Filipa Maria Rodrigues Pardal • Ferreira Llorente Grancho Lourenco, Sara
Assignees
Technophage Investigacao e Desenvolvimento em Biotecnologia SA
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Abstract
The present invention is directed to the field of phage therapy for the treatment and control of bacterial infections. In particular, the present invention is directed to the novel bacteriophages F1245/05, F168/08, F170/08, F770/05, F197/08, F86/06, F87s/06 and F91a/06, isolated polypeptides thereof, compositions comprising one or more of the novel bacteriophages and/or isolated polypeptides and methods for the treatment and prevention of bacterial infection, either alone or in combination with other antibacterial therapies, e.g., antibiotics or other phage therapies.
Core Innovation
The invention relates to phage therapy comprising novel bacteriophages and isolated bacteriophage polypeptides for treating or preventing bacterial infections. The disclosed bacteriophages include phage types identified as F1245/05, F168/08, F170/08, F770/05, F197/08, F86/06, F87s/06, and F91a/06, and are provided as purified bacteriophages and sequence-id defined embodiments. The invention further provides pharmaceutical compositions comprising a pharmaceutically acceptable carrier and the bacteriophage and/or the isolated polypeptides.
The invention targets nosocomial pathogens including Acinetobacter baumannii, Enterococcus faecalis and Enterococcus faecium, Pseudomonas aeruginosa, and Staphylococcus aureus, including MRSA. It is described that the bacteriophages and polypeptides have antibacterial activity against the target pathogens, including at least 99% sequence identity to nucleotide sequence embodiments defined by SEQ ID NOs. The isolated bacteriophage polypeptides include endolysins/CHAP domains and tail proteins, including tail length tape measure protein and other tail proteins.
In addition to therapeutic uses, the document describes diagnostic identification using phage/polypeptide susceptibility, including concepts based on sequence-id defined phage and polypeptide embodiments. The disclosed embodiments include genomes and polypeptides defined by SEQ ID NOs and sequence identity ranges, including polypeptide variants, fragments, and derivatives. The document also describes roles of CHAP domains and sequence variants as part of the disclosed polypeptide embodiments.
Claims Coverage
The document includes at least one independent claim focused on treating or reducing the incidence of an Acinetobacter baumannii bacterial infection by administering a pharmaceutical composition together with a purified bacteriophage defined by sequence identity and antibacterial activity. Dependent claims further refine the patient indication and administration route and may optionally add co-therapy.
Treating or reducing incidence of Acinetobacter baumannii infection with sequence-identified purified bacteriophage and pharmaceutical composition
A method of treating or reducing the incidence of an Acinetobacter baumannii bacterial infection in a subject in need thereof by administering an effective amount of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a purified bacteriophage having at least 99% sequence identity to the nucleotide sequence of SEQ ID NO:760 and having antibacterial activity against Acinetobacter baumannii.
The claim coverage is centered on administering an effective amount of a pharmaceutical composition plus a purified bacteriophage that is defined by high nucleotide sequence identity to SEQ ID NO:760 and by antibacterial activity against Acinetobacter baumannii. Dependent claims further refine the infection type and administration route, and optionally include additional co-therapy with an antibiotic or another bacteriophage with relevant antibacterial/antimicrobial activity.
Stated Advantages
Treating or reducing the incidence of an Acinetobacter baumannii bacterial infection in a subject in need thereof.
Allows antibacterial activity against Acinetobacter baumannii using a purified bacteriophage defined by at least 99% sequence identity to SEQ ID NO:760.
Documented Applications
Treatment or reduction of incidence of Acinetobacter baumannii bacterial infection in a subject in need thereof.
Nosocomial pneumonia; urinary tract infections; cerebrospinal fluid infection or nosocomial meningitis; peritoneal fluid infections; infections associated with surgical drains/catheterization/CAPD; skin infections such as diabetic foot ulcer.
Diagnostic identification via phage/polypeptide susceptibility (sequence-id based diagnostic concepts).
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